Specialized stellate cells offer a privileged route for rapid water flux in Drosophila renal tubule

Insects are highly successful, in part through an excellent ability to osmoregulate. The renal (Malpighian) tubules can secrete fluid faster on a per-cell basis than any other epithelium, but the route for these remarkable water fluxes has not been established. In Drosophila melanogaster, we show that 4 genes of the major intrinsic protein family are expressed at a very high level in the fly renal tissue: the aquaporins (AQPs) Drip and Prip and the aquaglyceroporins Eglp2 and Eglp4. As predicted from their structure, and by their transport function by expressing these proteins in Xenopus oocytes, Drip, Prip, and Eglp2 show significant and specific water permeability, whereas Eglp2 and Eglp4 show very high permeability to glycerol and urea. Knockdowns of any of these genes result in impaired hormone-induced fluid secretion. The Drosophila tubule has 2 main secretory cell types: active cation-transporting principal cells, wherein the aquaglyceroporins localize to opposite plasma membranes, and small stellate cells, the site of the chloride shunt conductance, with these AQPs localizing to opposite plasma membranes. This suggests a model in which osmotically obliged water flows through the stellate cells. Consistent with this model, fluorescently labeled dextran, an in vivo marker of membrane water permeability, is trapped in the basal infoldings of the stellate cells after kinin diuretic peptide stimulation, confirming that these cells provide the major route for transepithelial water flux. The spatial segregation of these components of epithelial water transport may help to explain the unique success of the higher insects in regulating their internal environments

Participatory Mapping to Address Neighborhood Level Data Deficiencies for food Security Assessment in Southeastern Virginia, USA

Background: Food is not equitably available. Deficiencies and generalizations limit national datasets, food security assessments, and interventions. Additional neighborhood level studies are needed to develop a scalable and transferable process to complement national and internationally comparative data sets with timely, granular, nuanced data. Participatory geographic information systems (PGIS) offer a means to address these issues by digitizing local knowledge. Methods: The objectives of this study were two-fold: (i) identify granular locations missing from food source and risk datasets and (ii) examine the relation between the spatial, socio-economic, and agency contributors to food security. Twenty-nine subject matter experts from three cities in Southeastern Virginia with backgrounds in food distribution, nutrition management, human services, and associated research engaged in a participatory mapping process. Results: Results show that publicly available and other national datasets are not inclusive of non-traditional food sources or updated frequently enough to reflect changes associated with closures, expansion, or new programs. Almost 6 percent of food sources were missing from publicly available and national datasets. Food pantries, community gardens and fridges, farmers markets, child and adult care programs, and meals served in community centers and homeless shelters were not well represented. Over 24 km2 of participant identified need was outside United States Department of Agriculture low income, low access areas. Economic, physical, and social barriers to food security were interconnected with transportation limitations. Recommendations address an international call from development agencies, countries, and world regions for intervention methods that include systemic and generational issues with poverty, incorporate non-traditional spaces into food distribution systems, incentivize or regulate healthy food options in stores, improve educational opportunities, increase data sharing. Conclusions: Leveraging city and regional agency as appropriate to capitalize upon synergistic activities was seen as critical to achieve these goals, particularly for non-traditional partnership building. To address neighborhood scale food security needs in Southeastern Virginia, data collection and assessment should address both environment and utilization issues from consumer and producer perspectives including availability, proximity, accessibility, awareness, affordability, cooking capacity, and preference. The PGIS process utilized to facilitate information sharing about neighborhood level contributors to food insecurity and translate those contributors to intervention strategies through discussion with local subject matter experts and contextualization within larger scale food systems dynamics is transferable

Cloning, function, and localization of human, canine, and Drosophila ZIP10 (SLC39A10), a Zn2+ transporter

Zinc (Zn2+) is the second most abundant trace element, but is considered a micronutrient, as it is a cofactor for many enzymes and transcription factors. Whereas Zn2+ deficiency can cause cognitive immune or metabolic dysfunction and infertility, excess Zn2+ is nephrotoxic. As for other ions and solutes, Zn2+ is moved into and out of cells by specific membrane transporters: ZnT, Zip, and NRAMP/DMT proteins. ZIP10 is reported to be localized at the apical membrane of renal proximal tubules in rats, where it is believed to play a role in Zn2+ import. Renal regulation of Zn2+ is of particular interest in light of growing evidence that Zn2+ may play a role in kidney stone formation. The objective of this study was to show that ZIP10 homologs transport Zn2+, as well as ZIP10, kidney localization across species. We cloned ZIP10 from dog, human, and Drosophila (CG10006), tested clones for Zn2+ uptake in Xenopus oocytes and localized the protein in renal structures. CG10006, rather than foi (fear-of-intimacy, CG6817) is the primary ZIP10 homolog found in Drosophila Malpighian tubules. The ZIP10 antibody recognizes recombinant dog, human, and Drosophila ZIP10 proteins. Immunohistochemistry reveals that ZIP10 in higher mammals is found not only in the proximal tubule, but also in the collecting duct system. These ZIP10 proteins show Zn2+ transport. Together, these studies reveal ZIP10 kidney localization, a role in renal Zn2+ transport, and indicates that CG10006 is a Drosophila homolog of ZIP10

Increased Risk of Genetic and Epigenetic Instability in Human Embryonic Stem Cells Associated with Specific Culture Conditions

The self-renewal and differentiation capacities of human pluripotent stem cells (hPSCs) make them a promising source of material for cell transplantation therapy, drug development, and studies of cellular differentiation and development. However, the large numbers of cells necessary for many of these applications require extensive expansion of hPSC cultures, a process that has been associated with genetic and epigenetic alterations. We have performed a combinatorial study on both hESCs and hiPSCs to compare the effects of enzymatic vs. mechanical passaging, and feeder-free vs. mouse embryonic fibroblast feeder substrate, on the genetic and epigenetic stability and the phenotypic characteristics of hPSCs. In extensive experiments involving over 100 continuous passages, we observed that both enzymatic passaging and feeder-free culture were associated with genetic instability, higher rates of cell proliferation, and persistence of OCT4/POU5F1-positive cells in teratomas, with enzymatic passaging having the stronger effect. In all combinations of culture conditions except for mechanical passaging on feeder layers, we noted recurrent deletions in the genomic region containing the tumor suppressor gene TP53, which was associated with decreased mRNA expression of TP53, as well as alterations in the expression of several downstream genes consistent with a decrease in the activity of the TP53 pathway. Among the hESC cultures, we also observed culture-associated variations in global gene expression and DNA methylation. The effects of enzymatic passaging and feeder-free conditions were also observed in hiPSC cultures. Our results highlight the need for careful assessment of the effects of culture conditions on cells intended for clinical therapies

The Application of Novel Research Technologies by the Deep Pelagic Nekton Dynamics of the Gulf of Mexico (DEEPEND) Consortium

The deep waters of the open ocean represent a major frontier in exploration and scientific understanding. However, modern technological and computational tools are making the deep ocean more accessible than ever before by facilitating increasingly sophisticated studies of deep ocean ecosystems. Here, we describe some of the cutting-edge technologies that have been employed by the Deep Pelagic Nekton Dynamics of the Gulf of Mexico (DEEPEND; www.deependconsortium.org) Consortium to study the biodiverse fauna and dynamic physical-chemical environment of the offshore Gulf of Mexico (GoM) from 0 to 1,500 m

All Our Babies Cohort Study: recruitment of a cohort to predict women at risk of preterm birth through the examination of gene expression profiles and the environment

<p>Abstract</p> <p>Background</p> <p>Preterm birth is the leading cause of perinatal morbidity and mortality. Risk factors for preterm birth include a personal or familial history of preterm delivery, ethnicity and low socioeconomic status yet the ability to predict preterm delivery before the onset of preterm labour evades clinical practice. Evidence suggests that genetics may play a role in the multi-factorial pathophysiology of preterm birth. The All Our Babies Study is an on-going community based longitudinal cohort study that was designed to establish a cohort of women to investigate how a women's genetics and environment contribute to the pathophysiology of preterm birth. Specifically this study will examine the predictive potential of maternal leukocytes for predicting preterm birth in non-labouring women through the examination of gene expression profiles and gene-environment interactions.</p> <p>Methods/Design</p> <p>Collaborations have been established between clinical lab services, the provincial health service provider and researchers to create an interdisciplinary study design for the All Our Babies Study. A birth cohort of 2000 women has been established to address this research question. Women provide informed consent for blood sample collection, linkage to medical records and complete questionnaires related to prenatal health, service utilization, social support, emotional and physical health, demographics, and breast and infant feeding. Maternal blood samples are collected in PAXgene™ RNA tubes between 18-22 and 28-32 weeks gestation for transcriptomic analyses.</p> <p>Discussion</p> <p>The All Our Babies Study is an example of how investment in clinical-academic-community partnerships can improve research efficiency and accelerate the recruitment and data collection phases of a study. Establishing these partnerships during the study design phase and maintaining these relationships through the duration of the study provides the unique opportunity to investigate the multi-causal factors of preterm birth. The overall All Our Babies Study results can potentially lead to healthier pregnancies, mothers, infants and children.</p

DNA Methylation

<p><b>A</b>. X Chromosome DNA Methylation and XIST Expression. Methylation levels of genes in the X-chromosome (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0118307#pone.0118307.s009" target="_blank">S6A Table</a>) are shown on the heatmap. Hierarchical clustering was performed on the samples, as indicated by the dendrogram. The genes are ordered according to their location (from the beginning to the end of the chromosome). Samples that show loss of DNA methylation for the “Enz” cluster are highlighted in blue, those that show DNA methylation for the “Ecm” cluster are highlighted in pink, and for both clusters in mauve. Genes located in the regions of loss of DNA methylation are listed to the right of the heatmap. XIST expression is shown on the line graph, with the detection limit for the microarray indicated by the red line. <b>B</b>. DNA methylation at imprinted loci. Methylation levels for imprinted probes (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0118307#pone.0118307.s009" target="_blank">S6B Table</a>) are shown on the heatmap. Hierarchical clustering was performed on the samples, as indicated by the dendrogram. The genes are ordered according to chromosome location; genes are listed to the left. The inset at the right shows a detail of the NESP/GNAS complex locus, indicating the positions of the CpG sites that were hypermethylated (red triangle) vs. hypomethylated (green triangle) in the late passage samples relative to the NESP/GNAS and NESPAS exons. <b>C, D, E</b>. Heatmaps showing differential DNA methylation genes for early vs. late passage <b>(C)</b>, mechanical vs. enzymatic passage <b>(D)</b>, and Mef vs. Ecm substrate <b>(E)</b>. In heatmap <b>(C)</b>, the black boxes indicate genes for which the DNA methylation levels in the late passage MefMech (P103) samples was more similar to those in the early passage samples. Probes were selected by multivariate regression. Functional enrichments identified by GREAT analysis are shown to the right of the heatmaps, visualized using REVIGO [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0118307#pone.0118307.ref013" target="_blank">13</a>]. Samples were arranged according to passage and culture method, and hierarchical clustering was performed on the genes only. In the functional enrichment results, the size of the node indicated the number of contributing GO terms, and color of the nodes indicates the FDR (darker color for lower FDR), and the edge length indicates the similarity between GO terms (shorter edge for more similar terms).</p

Déclaration sur l’approche par l’archéologie sociale du changement climatique

Manifiesto sobre Arqueología Social del Cambio Climático aprobado en la Cumbre SACC celebrada en Kiel. Aprobado y firmado el 6 de septiembre de 2021.[ES] El SACC es un grupo independiente, constituido en Kiel, de investigadores e investigadoras que trabajan sobre cambio climático. El objetivo de SACC es reunir científicos y científicas internacionales y representantes de importantes organizaciones internacionales de las áreas de arqueología, paleoecología y gestión del patrimonio para con el fin de discutir y evaluar la contribución de la investigación arqueológica y paleo-ecológica para comprender la interrelación entre el cambio social, el cultural, el ecológico y el climático. Pretendemos resaltar cómo la arqueología, a través del estudio de la conducta adaptativa en el pasado, es capaz de reforzar tanto la resiliencia socio-ecológica de nuestras sociedades, como su capacidad adaptativa ante el actual cambio climático. Además, pretendemos contribuir a la comprensión del impacto del cambio climático en los yacimientos y sitios arqueológicos y patrimoniales, así como en los paisajes culturales, los museos, las colecciones y archivos patrimoniales. SACC celebrará cumbres cada dos años y emitirá una declaración o manifiesto al término de cada una de ellas. S ACC está organizada por un comité interino presidido por las personas convocantes del SACC 1.[EN] SACC is an independent group of researchers working on climate change in the past constituted in Kiel. The aim of SACC is to bring together international scientists and representatives of important international organisations in the fields of archaeology, paleoecology and heritage management to discuss and evaluate the contribution of archaeological and paleo-ecological research to understand the link between social, cultural, ecological and climatic change; and to highlight how archaeology, through the study of past adaptive behaviour, is able to enhance socio-ecological resilience of societies as well as their adaptive capacity to current climate change; furthermore, to contribute to the understanding of the impact of climate change on archaeological and heritage sites as well as on cultural landscapes, museums, collections, and archives. SACC will hold its summit every second year with a declaration at the end of each summit. SACC is organized by a steering committee chaired by the SACC 1 organisers.[FR] Le SACC est un groupe indépendant de chercheurs travaillant sur le changement climatique dans le passé, qui s’est formé à Kiel. L’objectif du S ACC est de réunir des scientifiques internationaux et des représentants d’organisations internationales importantes dans les domaines de l’archéologie, de la paléoécologie et de la gestion du patrimoine. Il a pour objectif de discuter et d’évaluer la contribution de la recherche archéologique et paléo-écologique à la compréhension du lien entre les changements sociaux, culturels, écologiques et climatiques et de souligner comment l’archéologie, par l’étude du comportement adaptatif du passé, est capable d’améliorer la résilience socioécologique des sociétés ainsi que leur capacité d’adaptation au changement climatique actuel. En outre, il contribue à la compréhension de l’impact du changement climatique sur les sites archéologiques et patrimoniaux ainsi que sur les paysages culturels, les musées, les collections et les archives. Le SACC tiendra son conseil tous les deux ans avec une déclaration à la fin de chaque conseil. Il est organisé par un comité de pilotage présidé par les organisateurs de SACC 1.Peer reviewe

Unfolded protein response in cancer: the Physician's perspective

The unfolded protein response (UPR) is a cascade of intracellular stress signaling events in response to an accumulation of unfolded or misfolded proteins in the lumen of the endoplasmic reticulum (ER). Cancer cells are often exposed to hypoxia, nutrient starvation, oxidative stress and other metabolic dysregulation that cause ER stress and activation of the UPR. Depending on the duration and degree of ER stress, the UPR can provide either survival signals by activating adaptive and antiapoptotic pathways, or death signals by inducing cell death programs. Sustained induction or repression of UPR pharmacologically may thus have beneficial and therapeutic effects against cancer. In this review, we discuss the basic mechanisms of UPR and highlight the importance of UPR in cancer biology. We also update the UPR-targeted cancer therapeutics currently in clinical trials